Patients with Diabetes Mellitus (DM) manifest an increased incidence of congestive heart failure (CHF) following myocardial infarction (MI), which presages a reduced survival rate. This has been shown not to be due to a greater extent of infarction associated with DM. The long-term goals of our studies is to understand the mechanisms that contribute to the progressive deterioration of cardiac function and eventual development of CHF in the diabetic heart following an MI. The current project is based on observations that hyperglycemia secondary to diabetes and non-diabetic post-MI heart failure are associated with increased oxidative stress and an antioxidant deficit. Based on these observations, we propose that the coexistence of diabetes and MI exacerbates the existing imbalance between the antioxidant defense system and free-radical production already present in each of these pathologies individually, leading to a quantitative deficiency of antioxidants that predisposes the surviving diabetic myocardium to cumulative, uncontrolled oxidant damage and subsequent failure after MI. The specific aims of the proposed project are: 1) to assess myocardial enzymatic and non-enzymatic antioxidants and concomitant oxidative stress in the remaining, viable diabetic myocardium after MI; 2) to determine the protein expression of the myocardial antioxidant enzymes, and 3) to determine the effects of long-term antioxidant therapy on the occurrence of heart failure following MI in the diabetic heart. The proposed studies will be conducted in streptozotocin (STZ)-induced diabetic rats using the well-established coronary-artery ligation model of post-MI heart failure. The objectives of these studies are to delineate the mechanisms by which diabetes adversely affects the functioning of the surviving myocardium after MI and to establish novel therapies aimed at reversing the functional deficit associated with diabetes during the post-MI period. The results of this project will provide a new understanding of the factors that contribute to CHF among diabetics with MI and may form the basis for developing more effective therapeutic interventions for the management of diabetic MI patients.